Rapid Report

Coexpression of KCNQ2 and KCNQ3 channels results in a 10‐fold increased current amplitude compared to that of KCNQ2 alone, suggesting the formation of heteromultimeric channels. There is no interaction of either channel with KCNQ1. We evaluated the C‐terminus as a potential interaction domain by construction of chimeras with interchanged C‐termini of KCNQ1, KCNQ2 and KCNQ3 and functional expression in Xenopus oocytes. The chimera of KCNQ1 with a KCNQ2 C‐terminus (Q1ctQ2) showed an 8‐fold increase in current amplitude, and Q1ctQ3 a 3‐fold increase when coexpressed with KCNQ3 and KCNQ2, respectively, indicating that the C‐terminus contains an interaction domain. To characterize this interacting region, we studied further chimeras of KCNQ1 containing different parts of the KCNQ3 C‐terminus for interaction with KCNQ2. We also evaluated short sequences of the KCNQ2 C‐terminus for a dominant‐negative effect on Q1ctQ3. According to the results of these experiments, functional interaction of KCNQ2 and KCNQ3 requires a highly conserved region of about 80 amino acids, previously called the A‐domain, plus either 40 residues downstream of the A‐domain (B‐domain) or the proximal C‐terminus between S6 and the A‐domain. Furthermore, the chimeras Q1ctQ3 and Q2ctQ3 showed > 10‐fold increased current amplitudes compared to KCNQ1 or KCNQ2 alone and a strong depolarizing shift of voltage‐dependent activation. The proximal part of the KCNQ3 C‐terminus was necessary to produce these effects. Our results indicate that specific parts of the C‐terminus enable the interaction between KCNQ2 and KCNQ3 channels and that different parts of the KCNQ3 C‐terminus are important for regulating current amplitude.